11-62575346-C-T

Variant names:

• chr11-62575346-C-T
• rs36080058
• NM_022830.3:c.2373G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_022830.3(TUT1):​c.2373G>A​(p.Glu791Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,614,082 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (21 hom.)
• Consequence: TUT1 NM_022830.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.511
• Publications: 1 publications found

Genes affected

TUT1 (HGNC:26184): (terminal uridylyl transferase 1, U6 snRNA-specific) This gene encodes a nucleotidyl transferase that functions as both a terminal uridylyltransferase and a nuclear poly(A) polymerase. The encoded enzyme specifically adds and removes nucleotides from the 3' end of small nuclear RNAs and select mRNAs and may function in controlling gene expression and cell proliferation.[provided by RefSeq, Apr 2009]

ENSG00000255508 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-62575346-C-T is Benign according to our data. Variant chr11-62575346-C-T is described in ClinVar as Benign. ClinVar VariationId is 713413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.511 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00853 (1299/152344) while in subpopulation AFR AF = 0.0293 (1220/41580). AF 95% confidence interval is 0.028. There are 28 homozygotes in GnomAd4. There are 611 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 28 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022830.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUT1	NM_022830.3	MANE Select	c.2373G>A	p.Glu791Glu	synonymous	Exon 9 of 9	NP_073741.3	Q9H6E5
	TUT1	NM_001367906.1		c.*787G>A		3_prime_UTR	Exon 9 of 9	NP_001354835.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUT1	ENST00000476907.6	TSL:1 MANE Select	c.2373G>A	p.Glu791Glu	synonymous	Exon 9 of 9	ENSP00000419607.1	Q9H6E5
	TUT1	ENST00000308436.11	TSL:1	c.2487G>A	p.Glu829Glu	synonymous	Exon 9 of 9	ENSP00000308000.7	F5H0R1
	ENSG00000255508	ENST00000496634.2	TSL:2	n.1475-438G>A		intron	N/A	ENSP00000456163.1	H3BRB1

Frequencies

GnomAD3 genomes AF: 0.00842 AC: 1282 AN: 152226 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00241 AC: 606 AN: 251294 AF XY: 0.00183

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00108 AC: 1576 AN: 1461738 Hom.: 21 Cov.: 31 AF XY: 0.00101 AC XY: 731 AN XY: 727166

African (AFR) AF: 0.0315 AC: 1054 AN: 33480

American (AMR) AF: 0.00165 AC: 74 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00203 AC: 175 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0000665 AC: 74 AN: 1112012

Other (OTH) AF: 0.00310 AC: 187 AN: 60396

GnomAD4 genome AF: 0.00853 AC: 1299 AN: 152344 Hom.: 28 Cov.: 32 AF XY: 0.00820 AC XY: 611 AN XY: 74494

African (AFR) AF: 0.0293 AC: 1220 AN: 41580

American (AMR) AF: 0.00301 AC: 46 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00427 Hom.: 7

Bravo AF: 0.00998

Asia WGS AF: 0.00635 AC: 22 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.22
DANN	Benign	0.75
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36080058; hg19: chr11-62342818;